Carbohydrate-based, and particularly oligosaccharide-based, drugs and vaccines are attracting increasing attention because of the enormous potential they offer for the treatment of a broad range of disease states. This potential derives, at least in part, from the intimate involvement of carbohydrates in many biological processes including, inter alia, cell-to-cell recognition, cell adhesion, neural cell development and tumour metastasis. Whilst developments in this therapeutic area continue apace, the presence of glycosidic linkages in most of such compounds renders them vulnerable to hydrolytic cleavage. As a consequence they often posses unfavourable metabolic profiles that may restrict their use in, for example, oral applications. In principle, such problems might be overcome by employing glycominmetics particularly those embodying pseudo-sugars (wherein a pyranosyl- or furanosyl-ring oxygen has been replaced by a methylene unit) or related cyclitols in place of one or more of the “normal” monosaccharide residues. Despite the consequent potential of pseudo-sugars and cyclitols, remarkably few oligosaccharide analogues incorporating more than one such residue are known.
The applicant has previously identified a range of sulfated oligosaccharides with efficacy as, inter alia, anti-angiogenic, anti-proliferative and anti-thrombotic agents. One sulfated oligo-saccharide was found to be particularly potent and is now undergoing clinical trials. This oligosaccharide is phosphomannopentaose sulfate (hereafter “PI-88”) and is described in International Patent Application No. PCT/AU96/00238 (Publication No. WO 96/33726). The utility of PI-88 as an anti-angiogenic, anti-proliferative and anti-thrombotic agent is also described in WO 96/33726 while other indications of PI-88 and related sulfated oligo-saccharides are given in the international applications by the present applicant having the application numbers PCT/AU98/00151 (Publication No. WO 98/40081) and PCT/AU98/00707 (Publication No. WO 99/11273).
With regard to pseudo-sugars and cyclitols, B. J. Paul, T. A. Martinot, J. Willis and T. Hudlicky in Synthesis, 2001, p 952, reported the preparation of novel O- and N-linked inositol oligomers by chemoenzymatic means and highlighted the potential of these products as a new class of unnatural saccharide mimics. The inventors considered, in the light of this work by Paul et al., that it might be possible to develop methods for the rapid construction of other linked cyclitols, particularlypseudo-sugar based analogues of PI-88.